MicroRNA expression profile of bromocriptine-resistant prolactinomas

• A miRNA expression profile associated with bromocriptine-resistant prolactinoma.
• miRNA-93 regulates the sensitivity of MMQ cells to dopamine agonist treatment.
• P21 is the direct target of miRNA-93.
• These findings provide useful targets for development of miRNA-based therapies.

MicroRNAs (miRNA) have been implicated in the resistance of tumors to chemotherapy. However, little is known about miRNA expression in bromocriptine-resistant prolactinomas. In this study, 23 prolactinoma samples were classified as bromocriptine-sensitive or -resistant according to the clinical definition of bromocriptine resistance, and their miRNA expression profiles were determined using Solexa sequencing. We found 41 miRNAs that were differentially expressed between the two groups, and 12 of these were validated by stem-loop qRT-PCR. Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas. Furthermore, silencing of mir-93 significantly increased the sensitivity of MMQ cells to dopamine agonist treatment. Mir-93 directly affected p21 expression in MMQ cells by targeting the 3′-UTR. Our study is the first to identify a miRNA expression profile associated with bromocriptine-resistant prolactinoma.